Pancreatology最新文献

{"title":"Diagnosis of pancreatic malignancies using an overnight-stored pancreatic juice cell block specimen","authors":"Mitsuru Okuno ,&nbsp;Takuji Tanaka ,&nbsp;Keisuke Iwata ,&nbsp;Tsuyoshi Mukai ,&nbsp;Naoki Watanabe ,&nbsp;Kota Shimojo ,&nbsp;Yuhei Iwasa ,&nbsp;Ryuichi Tezuka ,&nbsp;Takuji Iwashita ,&nbsp;Eiichi Tomita ,&nbsp;Masahito Shimizu","doi":"10.1016/j.pan.2024.06.005","DOIUrl":"10.1016/j.pan.2024.06.005","url":null,"abstract":"<div><h3>Background and aims</h3><p>Pancreatic juice cytology is useful for diagnosing pancreatic duct strictures and cystic lesions. However, some cases cannot be diagnosed using cytology. This study aimed to evaluate the utility of the overnight-stored pancreatic juice cell block (CB) method for diagnosing pancreatic disease.</p></div><div><h3>Methods</h3><p>This retrospective study included 32 patients who presented with pancreatic duct strictures or cystic lesions between 2018 and 2024. The sensitivity, specificity, and accuracy of the CB method and single/multiple pancreatic juice cytology were compared to evaluate the utility of the CB.</p></div><div><h3>Result</h3><p>An endoscopic nasopancreatic drainage tube was placed in the main pancreatic duct, and pancreatic juice was collected to create a CB specimen. The median amount of pancreatic juice collected was 180(30–200) mL, and the median number of cytological examinations was three(2–8). Of the 32 cases, 13 were malignant, and 19 were benign (non-malignant). The sensitivity was significantly higher for the CB method (62 %) than for single cytology(15 %, <em>P</em> = 0.0414), and there was no significant difference between CB and multiple cytology(54 %, <em>P</em> = 1.0). The specificity and accuracy were not significantly different between the CB method and single or multiple cytology. When multiple cytology and CB were combined, sensitivity improved to 77 %. The pathological findings of the CB specimens were similar to the surgical specimens, including immunohistochemistry.</p></div><div><h3>Conclusion</h3><p>The overnight-stored pancreatic juice CB method was more effective than single cytology, with similar sensitivities to multiple cytology and can also be used for immunohistochemistry. The pancreatic juice CB method is useful for pancreatic juice assessment.</p></div>","PeriodicalId":19976,"journal":{"name":"Pancreatology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141327773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pancreatic juice cytology for diagnosing invasive pancreatic carcinoma/high-grade pancreatic intraepithelial neoplasia without visible tumors on endoscopic ultrasound","authors":"Ryota Sagami ,&nbsp;Kazuhiro Mizukami ,&nbsp;Hidefumi Nishikiori ,&nbsp;Takao Sato ,&nbsp;Shozo Fujiwara ,&nbsp;Yusuke Kawamoto ,&nbsp;Yusuke Ome ,&nbsp;Goro Honda ,&nbsp;Shin-ichiro Horiguchi ,&nbsp;Keiji Sato ,&nbsp;Kazunari Murakami","doi":"10.1016/j.pan.2024.06.006","DOIUrl":"10.1016/j.pan.2024.06.006","url":null,"abstract":"<div><h3>Objectives</h3><p>Pancreatic ductal adenocarcinoma (PDAC) with a diameter ≤10 mm and high-grade pancreatic intraepithelial neoplasia (HG-PanIN) require pre-operative diagnosis. Most cases present only indirect imaging findings without visible tumors on endoscopic ultrasound (EUS). Therefore, EUS-guided fine-needle aspiration/biopsy is not applicable. An alternative diagnostic method is pancreatic juice cytology (PJC) via endoscopic naso-pancreatic drainage (ENPD-PJC), which is not the standard practice. This study aimed to investigate ENPD-PJC for diagnosing suspected PDAC/HG-PanIN cases without visible tumors on EUS.</p></div><div><h3>Methods</h3><p>Data of patients with suspected PDAC/HG-PanIN without visible tumors who underwent PJC were retrospectively evaluated. One PJC sample was collected during endoscopic retrograde pancreatography (ERP-PJC), and 12 samples were collected during ENPD-PJC, 3-hourly for cytological analysis. ERP-PJC, ERP/ENPD-PJC, and ENPD-PJC positivity indicated cytologically positive samples. Patients with positive/negative PJC with follow-up for &lt;4-years were excluded as undiagnosed cases. A non-malignant diagnosis was based on histopathological absence/stable imaging findings for ≥4-years. The primary endpoint was to demonstrate that ERP/ENPD-PJC has a higher diagnostic ability than ERP-PJC.</p></div><div><h3>Results</h3><p>Twenty-two patients with histopathologically diagnosed PDAC/HG-PanIN and 31 with a non-malignant diagnosis were enrolled. ERP-PJC, ERP/ENPD-PJC, and ENPD-PJC showed sensitivities of 36.4 %, 86.4 %, and 77.3 %, specificities of 93.5 %, 87.1 %, and 93.5 %, and accuracies of 69.8 %, 86.7 %, and 86.7 %, respectively. ERP/ENPD-PJC and ENPD-PJC demonstrated superior sensitivity and accuracy compared to ERP-PJC. A greater occurrence of positive outcomes markedly distinguished true positives from false positives.</p></div><div><h3>Conclusions</h3><p>ERP/ENPD-PJC and ENPD-PJC had higher diagnostic accuracies for PDAC/HG-PanIN without visible tumors on EUS. ENPD-PJC is recommended for the diagnosis of these lesions.</p></div>","PeriodicalId":19976,"journal":{"name":"Pancreatology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1424390324006616/pdfft?md5=829ccd3ca8e17417705a2698a86199e8&pid=1-s2.0-S1424390324006616-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141415604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel chymotrypsin C (CTRC) variants from real-world genetic testing of pediatric chronic pancreatitis cases","authors":"Regina Stefanovics ,&nbsp;Máté Sándor ,&nbsp;Alexandra Demcsák ,&nbsp;Gergő Berke ,&nbsp;Balázs Csaba Németh ,&nbsp;Wenying Zhang ,&nbsp;Maisam Abu-El-Haija ,&nbsp;Miklós Sahin-Tóth","doi":"10.1016/j.pan.2024.06.003","DOIUrl":"10.1016/j.pan.2024.06.003","url":null,"abstract":"<div><h3>Background</h3><p>Chymotrypsin C (CTRC) protects the pancreas against unwanted intrapancreatic trypsin activity through degradation of trypsinogen. Loss-of-function <em>CTRC</em> variants increase the risk for chronic pancreatitis (CP). The aim of the present study was to characterize novel <em>CTRC</em> variants found during genetic testing of CP cases at a pediatric pancreatitis center.</p></div><div><h3>Methods</h3><p>We used next-generation sequencing to screen patients. We analyzed the functional effects of <em>CTRC</em> variants in HEK 293T cells and using purified enzymes.</p></div><div><h3>Results</h3><p>In 5 separate cases, we detected 5 novel heterozygous <em>CTRC</em> variants: c.407C&gt;T (p.Thr136Ile), c.550G&gt;A (p.Ala184Thr), c.627Cdup (p.Ser210Leufs∗?, where the naming indicates a frame shift with no stop codon), c.628T&gt;C (p.Ser210Pro), and c.779A&gt;G (p.Asp260Gly). Functional studies revealed that with the exception of p.Ser210Leufs∗?, the <em>CTRC</em> variants were secreted normally from transfected cells. Enzyme activity of purified variants p.Thr136Ile, p.Ala184Thr, and p.Asp260Gly was similar to that of wild-type CTRC, whereas variant p.Ser210Pro was inactive. The frame-shift variant p.Ser210Leufs∗? was not secreted but accumulated intracellularly, and induced endoplasmic reticulum stress, as judged by elevated mRNA levels of <em>HSPA5</em> and <em>DDIT3</em>, and increased mRNA splicing of <em>XBP1</em>.</p></div><div><h3>Conclusions</h3><p><em>CTRC</em> variants p.Ser210Pro and p.Ser210Leufs∗? abolish CTRC function and should be classified as pathogenic. Mechanistically, variant p.Ser210Pro directly affects the amino acid at the bottom of the substrate-binding pocket while the frame-shift variant promotes misfolding and thereby blocks enzyme secretion. Importantly, 3 of the 5 novel <em>CTRC</em> variants proved to be benign, indicating that functional analysis is indispensable for reliable determination of pathogenicity and the correct interpretation of genetic test results.</p></div>","PeriodicalId":19976,"journal":{"name":"Pancreatology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141321374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of endoscopic ultrasound-guided tissue acquisition on prognosis and peritoneal lavage cytology in resectable or borderline resectable pancreatic ductal adenocarcinoma","authors":"Motonobu Maruo ,&nbsp;Tsukasa Ikeura ,&nbsp;Ayaka Takaori ,&nbsp;Masatoshi Ikeda ,&nbsp;Koh Nakamaru ,&nbsp;Takashi Ito ,&nbsp;Masataka Masuda ,&nbsp;Toshiyuki Mitsuyama ,&nbsp;Shinji Nakayama ,&nbsp;Masaaki Shimatani ,&nbsp;Makoto Takaoka ,&nbsp;Nobuhiro Shibata ,&nbsp;Shogen Boku ,&nbsp;Tomoyo Yasuda ,&nbsp;Hidetaka Miyazaki ,&nbsp;Kazuki Matsumura ,&nbsp;So Yamaki ,&nbsp;Daisuke Hashimoto ,&nbsp;Sohei Satoi ,&nbsp;Makoto Naganuma","doi":"10.1016/j.pan.2024.06.001","DOIUrl":"10.1016/j.pan.2024.06.001","url":null,"abstract":"<div><h3>Objectives</h3><p>This study aimed to evaluate the clinical impact of preoperative endoscopic ultrasound-guided tissue acquisition (EUS-TA) on the prognosis and incidence of positive peritoneal lavage cytology (PLC) during laparotomy or staging laparoscopy in patients with resectable (R) or borderline resectable (BR) pancreatic ductal adenocarcinoma (PDAC).</p></div><div><h3>Methods</h3><p>We retrospectively collected data from patients diagnosed with body and tail PDAC with/without EUS-TA at our hospital from January 2006 to December 2021.</p></div><div><h3>Results</h3><p>To examine the effect of EUS-TA on prognosis, 153 patients (122 in the EUS-TA group, 31 in the non-EUS-TA group) were analyzed. There was no significant difference in overall survival between the EUS-TA and non-EUS-TA groups after PDAC resection (<em>P</em> = 0.777). In univariate and multivariate analysis, preoperative EUS-TA was not identified as an independent factor related to overall survival after pancreatectomy [hazard ratio 0.96, 95 % confidence interval (CI) 0.54–1.70, <em>P</em> = 0.897]. Next, to examine the direct influence of EUS-TA on the results of PLC, 114 patients (83 in the EUS-TA group and 31 in the non-EUS-TA group) were analyzed. Preoperative EUS-TA was not statistically associated with positive PLC (odds ratio 0.73, 95 % CI 0.25–2.20, <em>P</em> = 0.583). After propensity score matching, overall survival and positive PLC were the same in both groups.</p></div><div><h3>Conclusions</h3><p>EUS-TA had no negative impact on postoperative survival and PLC-positive rates in R/BR PDAC.</p></div>","PeriodicalId":19976,"journal":{"name":"Pancreatology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141317872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Usefulness of pancreatic volume quantitative analysis as a predictor of development and severity of post-endoscopic retrograde cholangiopancreatography pancreatitis","authors":"Yu Akazawa,&nbsp;Masahiro Ohtani,&nbsp;Takuto Nosaka,&nbsp;Kazuto Takahashi,&nbsp;Tatsushi Naito,&nbsp;Hidetaka Matsuda,&nbsp;Yasunari Nakamoto","doi":"10.1016/j.pan.2024.06.002","DOIUrl":"10.1016/j.pan.2024.06.002","url":null,"abstract":"<div><h3>Background</h3><p>Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) is one of the most common and serious adverse events associated with ERCP. Thus, we aimed to investigate the usefulness of pre-ERCP pancreatic volume, which is deeply involved in exocrine pancreatic function, as a predictor of PEP development and severity.</p></div><div><h3>Methods</h3><p>In total, 1107 patients who underwent their first ERCP were recruited from January 2012 to December 2022 for this retrospective study. Pancreatic volume was measured by cross-sectional analysis using pre-ERCP computed tomography images. The potential risk factors for PEP were analyzed using multivariate logistic regression.</p></div><div><h3>Results</h3><p>Of the 745 patients included in the study, 34 (4.6 %) developed PEP: severe, moderate, or mild PEP in 1, 7, and 26 cases, respectively. Multivariate analysis revealed that only a large pancreatic volume (&gt;70 cm³) was an independent risk factor for the development of PEP (odds ratio, 7.98; 95 % confidence interval, 11.80–67.50; <em>P</em> &lt; 0.001). Additionally, the incidence of PEP was significantly higher in patients with a pancreatic volume &gt;70 cm³ than in those with a pancreatic volume ≤70 cm³ (18.5 % [31/168] vs. 0.5 % [3/577]; <em>P</em> &lt; 0.001). Also, the association between the pre-ERCP pancreatic volume and PEP severity was positively correlated (r = 0.625, <em>P</em> &lt; 0.005), with a larger pancreatic volume corresponding to increased PEP severity.</p></div><div><h3>Conclusions</h3><p>A large pancreatic volume before ERCP may be a novel risk factor for PEP incidence and severity. This finding suggests that quantitative analysis of the pre-ERCP pancreatic volume could be a useful predictor of PEP.</p></div>","PeriodicalId":19976,"journal":{"name":"Pancreatology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141276473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SLC7A11 and the glutathione pathway as novel prognostic markers in resectable pancreatic ductal adenocarcinoma: A metabolomics study of clinical specimens","authors":"Hiroki Ohya ,&nbsp;Kentaro Miyake ,&nbsp;Hironori Fukuoka ,&nbsp;Masanori Oshi ,&nbsp;Atsushi Ishibe ,&nbsp;Koji Narita ,&nbsp;Ken Kasahara ,&nbsp;Itaru Endo","doi":"10.1016/j.pan.2024.05.530","DOIUrl":"10.1016/j.pan.2024.05.530","url":null,"abstract":"<div><h3>Background/objectives</h3><p>Despite the poor prognosis associated with pancreatic ductal adenocarcinoma (PDAC), there remains a lack of clarity regarding the metabolic pathways and their significant impact on its phenotype. Therefore, we aimed to utilize metabolomics to capture changes in clinical PDAC tissues and elucidate the significant metabolic pathways close to its phenotypes.</p></div><div><h3>Methods</h3><p>This basic research was retrospectively validated using database research, immunohistochemistry, and protein analysis based on the findings obtained from metabolomics using clinical tissues collected from prospectively registered patients with PDAC. mRNA expression analysis using a database and protein analysis using archived clinical specimens was performed to validate the candidate pathways identified using metabolomics. Between-group comparisons were analyzed using paired <em>t</em>-tests and log-rank test, and Kaplan–Meier curves illustrated survival times.</p></div><div><h3>Results</h3><p>Patients subjected to metabolomics revealed a significant increase in glutathione disulfide levels in PDAC tissues when compared to normal pancreatic tissues. The Cancer Genome Atlas database analysis revealed significant changes in glutathione pathway-related mRNAs in PDAC compared to that in the normal pancreas. Protein analysis of previously resected specimens demonstrated a significant increase in SLC7A11 expression in PDAC tissues. The abundance ratio of SLC7A11 isoforms was associated with the post-operative prognosis in resectable PDAC.</p></div><div><h3>Conclusion</h3><p>Glutathione disulfide levels were significantly increased in clinical PDAC metabolomics. Additionally, increased mRNA and protein expression in SLC7A11 was observed in PDAC. Furthermore, the SLC7A11 isoform abundance ratio may be a valuable prognostic marker in patients with resectable PDAC.</p></div>","PeriodicalId":19976,"journal":{"name":"Pancreatology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141280805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Contrast-enhanced endoscopic ultrasound likely does not improve diagnostic adequacy during endoscopic ultrasound guided tissue acquisition: A systematic review and meta-analysis","authors":"Marie Anne Engh ,&nbsp;Brigitta Teutsch ,&nbsp;Alexander Schulze Wenning ,&nbsp;Yael Hadani ,&nbsp;Omer Almog ,&nbsp;Dániel Sándor Veres ,&nbsp;Péter Hegyi ,&nbsp;Bálint Erőss","doi":"10.1016/j.pan.2024.04.007","DOIUrl":"10.1016/j.pan.2024.04.007","url":null,"abstract":"<div><h3>Background and aims</h3><p>Solid pancreatic masses are sampled through tissue acquisition by endoscopic ultrasound (EUS). Inadequate samples may significantly delay diagnosis, increasing costs and carrying risks to the patients. Aim: assess the diagnostic adequacy of tissue acquisition using contrast-enhanced harmonic endoscopic ultrasound (CEH-EUS) compared to conventional EUS.</p></div><div><h3>Methods</h3><p>Five databases (PubMed, Embase, CENTRAL, Scopus and Web of Science) were searched in November 2023. Studies comparing diagnostic adequacy, accuracy and safety using CEH-EUS versus conventional EUS for tissue acquisition of solid pancreatic masses were included. Risk of bias was assessed using the Risk of Bias tool for randomized controlled trials (RoB2) and the Risk Of Bias In Non-Randomized Studies - of Interventions (ROBINS-I) tool for non-randomized studies, level of evidence using the GRADE approach, Odds Ratios (RR) with 95 % Confidence Intervals (CI) calculated and pooled using a random-effects model. I² quantified heterogeneity.</p></div><div><h3>Results</h3><p>The search identified 3858 records; nine studies (1160 patients) were included. OR for achieving an adequate sample was 1.467 (CI: 0.850–2.533), for randomized trials 0.902 (CI: 0.541–1.505), for non-randomized 2.396 (CI: 0.916–6.264), with significant subgroup difference. OR for diagnostic accuracy was 1.326 (CI: 0.890–1977), for randomized trials 0.997 (CI: 0.593–1.977) and for non-randomized studies 1.928 (CI: 1.096–3.393), significant subgroup difference (p = 0.0467). No differences were observed for technical failures or adverse events. Heterogeneity was low, risk of bias “low” to “some concerns” for most outcomes, mostly moderate for non-randomized studies.</p></div><div><h3>Conclusion</h3><p>Non-randomized studies indicated differences in favor of contrast-enhanced EUS, randomized studies showed no difference in diagnostic adequacy, accuracy or sensitivity when using CEH-EUS.</p></div>","PeriodicalId":19976,"journal":{"name":"Pancreatology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1424390324001054/pdfft?md5=519e7d909b39fbb97b8faed596de56e9&pid=1-s2.0-S1424390324001054-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140775785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the enigmatic association between PNLIP variants and risk of chronic pancreatitis in a large Chinese cohort","authors":"Brett M. Cassidy ,&nbsp;Fei Jiang ,&nbsp;Jianguo Lin ,&nbsp;Jian-Min Chen ,&nbsp;Grace E. Curry ,&nbsp;Guo-Xiu Ma ,&nbsp;Steven J. Wilhelm ,&nbsp;Shun-Jiang Deng ,&nbsp;Guoying Zhu ,&nbsp;Zhuan Liao ,&nbsp;Mark E. Lowe ,&nbsp;Xunjun K. Xiao ,&nbsp;Wen-Bin Zou","doi":"10.1016/j.pan.2024.03.002","DOIUrl":"10.1016/j.pan.2024.03.002","url":null,"abstract":"<div><h3>Background &amp; Aims</h3><p>Protease-sensitive <em>PNLIP</em> variants were recently associated with chronic pancreatitis (CP) in European populations. The pathological mechanism yet remains elusive. Herein, we performed a comprehensive genetic and functional analysis of <em>PNLIP</em> variants found in a large Chinese cohort, aiming to further unravel the enigmatic association of <em>PNLIP</em> variants with CP.</p></div><div><h3>Methods</h3><p>All coding and flanking intronic regions of the <em>PNLIP</em> gene were analyzed for rare variants by targeted next-generation sequencing in 1082 Chinese CP patients and 1196 controls. All novel missense variants were subject to analysis of secretion, lipase activity, and proteolytic degradation. One variant was further analyzed for its potential to misfold and induce endoplasmic reticulum (ER) stress. p.F300L, the most common <em>PNLIP</em> variant associated with CP, was used as a control.</p></div><div><h3>Results</h3><p>We identified 12 rare heterozygous <em>PNLIP</em> variants, with 10 being novel. The variant carrier frequency did not differ between the groups. Of them, only the variant p.A433T found in a single patient was considered pathologically relevant. p.A433T exhibited increased susceptibility to proteolytic degradation, which was much milder than p.F300L. Interestingly, both variants exhibited an increased tendency to misfold, leading to intracellular retention as insoluble aggregates, reduced secretion, and elevated ER stress.</p></div><div><h3>Conclusions</h3><p>Our genetic and functional analysis of <em>PNLIP</em> variants identified in a Chinese CP cohort suggests that the p.A433T variant and the previously identified p.F300L variant are not only protease-sensitive but also may be potentially proteotoxic. Mouse studies of the <em>PNLIP</em> p.F300L and p.A433T variants are needed to clarify their role in CP.</p></div>","PeriodicalId":19976,"journal":{"name":"Pancreatology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140107763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alterations in exocrine pancreatic function after acute pancreatitis","authors":"Joseph Bejjani ,&nbsp;Mitchell L. Ramsey ,&nbsp;Peter J. Lee ,&nbsp;Anna Evans Phillips ,&nbsp;Vikesh K. Singh ,&nbsp;Dhiraj Yadav ,&nbsp;Georgios I. Papachristou ,&nbsp;Phil A. Hart","doi":"10.1016/j.pan.2024.03.003","DOIUrl":"10.1016/j.pan.2024.03.003","url":null,"abstract":"<div><p>Exocrine pancreatic dysfunction (EPD) is a malabsorptive complication of pancreatic disorders that can lead to a host of symptoms ranging from flatulence to diarrhea and contribute to weight loss and metabolic bone disease. It is increasingly recognized to occur after acute pancreatitis (AP), including episodes with mild severity. The risk of developing EPD after AP is influenced by a range of factors, including the degree of acinar cell destruction and inflammation during AP, and persistent structural derangements following AP. In this article, we discuss the epidemiology, pathophysiology, and clinical management of EPD after AP while highlighting key knowledge gaps.</p></div>","PeriodicalId":19976,"journal":{"name":"Pancreatology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1424390324000632/pdfft?md5=10834e30b25ecb2b87440e671521ac37&pid=1-s2.0-S1424390324000632-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140108143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Indigo naturalis as a promising novel treatment for type 2 autoimmune pancreatitis","authors":"Ken Kamata,&nbsp;Masatoshi Kudo,&nbsp;Tomohiro Watanabe","doi":"10.1016/j.pan.2024.03.011","DOIUrl":"10.1016/j.pan.2024.03.011","url":null,"abstract":"","PeriodicalId":19976,"journal":{"name":"Pancreatology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140194417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}